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タイトル: | HTLV-1 modulates the frequency and phenotype of FoxP3+CD4+ T cells in virus-infected individuals. |
著者: | Satou, Yorifumi Utsunomiya, Atae Tanabe, Junko Nakagawa, Masanori Nosaka, Kisato Matsuoka, Masao |
著者名の別形: | 松岡, 雅雄 |
キーワード: | HTLV-1 ATL HAM/TSP FoxP3 Tax HBZ |
発行日: | 30-May-2012 |
出版者: | BioMed Central Ltd. |
誌名: | Retrovirology |
巻: | 9 |
論文番号: | 46 |
抄録: | [Background]HTLV-1 utilizes CD4 T cells as the main host cell and maintains the proviral load via clonal proliferation of infected CD4^+ T cells. Infection of CD4^+ T cells by HTLV-1 is therefore thought to play a pivotal role in HTLV-1-related pathogenicity, including leukemia/lymphoma of CD4^+ T cells and chronic inflammatory diseases. Recently, it has been reported that a proportion of HTLV-1 infected CD4^+ T cells express FoxP3, a master molecule of regulatory T cells. However, crucial questions remain unanswered on the relationship between HTLV-1 infection and FoxP3 expression. [Results]To investigate the effect of HTLV-1 infection on CD4^+ T-cell subsets, we used flow cytometry to analyze the T-cell phenotype and HTLV-1 infection in peripheral mononuclear cells (PBMCs) of four groups of subjects, including 23 HTLV-1-infected asymptomatic carriers (AC), 10 patients with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), 10 patients with adult T-cell leukemia (ATL), and 10 healthy donors. The frequency of FoxP3^+ cells in CD4^+ T cells in AC with high proviral load and patients with HAM/TSP or ATL was higher than that in uninfected individuals. The proviral load was positively correlated with the percentage of CD4^+ T cells that were FoxP3^+. The CD4^+FoxP3^+ T cells, themselves, were frequently infected with HTLV-1. We conclude that FoxP3^+ T- cells are disproportionately infected with HTLV-1 during chronic infection. We next focused on PBMCs of HAM/TSP patients. The expression levels of the T_[reg] associated molecules CTLA-4 and GITR were decreased in CD4+FoxP3+ T cells. Further we characterized FoxP3^+CD4^+ T-cell subsets by staining CD45RA and FoxP3, which revealed an increase in CD45RA−FoxP3^[low] non-suppressive T-cells. These findings can reconcile the inflammatory phenotype of HAM/TSP with the observed increase in frequency of FoxP3^+ cells. Finally, we analyzed ATL cells and observed not only a high frequency of FoxP3 expression but also wide variation in FoxP3 expression level among individual cases. [Conclusions]HTLV-1 infection induces an abnormal frequency and phenotype of FoxP3^+CD4^+ T cells. |
著作権等: | © 2012 Satou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
URI: | http://hdl.handle.net/2433/159469 |
DOI(出版社版): | 10.1186/1742-4690-9-46 |
PubMed ID: | 22647666 |
出現コレクション: | 学術雑誌掲載論文等 |
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